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New Trends in
Management of Severe Sepsis
Dr. M. HELMI AFIFI(MBBCh, MSc, MD, DHA)
Prof. of Anesthesia & Intensive Care
Menoufiya Faculty of Medicine, Egypt
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Sepsis: common, lethal, and expensive
• Major cause of morbidity and mortality
worldwide
• Kills ~ 1,400 people worldwide every day
• 400 000 ICU admission /y in USA
• Mortality rate 30–40%
• $50 billion per year in health care costs in USA
Angus DC et al, Crit Care Med 2001; 29[Suppl.]:S109
American Heart Association. Heart Disease and Stroke statistics 2006
Update
Severe Sepsis:
Comparative Incidence and Mortality
†National Center for Health Statistics, 2001. §American Cancer Society, 2001. *American Heart
Association. 2000. ‡Angus DC et al. Crit Care Med 2001
Incidence Mortality
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Infection
“A microbial phenomenon
due to invasion of host
tissue by microorganisms”
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Sepsis
“ Systemic host response to
invasive infection”
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"Except on few occasions,
the patient appears to die
from the body's response to
infection rather than from
it."
Sir William Osler – 1904
The Evolution of Modern Medicine
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Widespread inflammatory response to a
variety of severe clinical insults
Systemic Inflammatory Response Syndrome
(SIRS)
Others
Pancreatitis
Trauma
Burn
INFECTION
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Widespread inflammatory response to a
variety of severe clinical insults
Clinically recognized by the presence of
two or more of the following:
1. Temperature >38°C or <36°C
2. Heart rate > 90/min
3. RR > 20/min or PaCO2 <32 mmHg
4. WBC >12,000 cells/mm3, <4000 cells/mm3
Systemic Inflammatory Response Syndrome
(SIRS)
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SIRS + Evidence of infection
Sepsis
INFECTION SIRS
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Severe SepsisSepsis + Organ dysfunction
Infection SIRS
Acute Organ Dysfunction
Tachycardia
Hypotension
CVP
PAOP
Jaundice
Enzymes
Albumin
PT
Altered
Consciousness
Confusion
Psychosis
Tachypnea
PaO2 <70 mm Hg
SaO2 <90%
PaO2/FiO2 300
Oliguria
Anuria
Creatinine
Platelets
PT/APTT
Protein C
D-dimer
Balk. Crit Care Clin 2000;16:337-52
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Septic shock
Sepsis
+
Hypotension despite adequate fluid resuscitation
+
Hypoperfusion
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Septicemia
Sepsis that has an infection
in the bloodstream
itself
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1. Systemic Inflammatory Response Syndrome
(SIRS)
2. Sepsis (SIRS + infection)
3. Severe Sepsis (sepsis + end-organ damage)
4. Septic Shock (severe sepsis + hypotension
despite a fluid bolus)
ACCP/SCCM Consensus Conference 1991
Definitions
Bone RC, et al: Chest 1992; 101:1644 –1655
Crit Care Med 1992; 20:864
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Sepsis: Progressive Disease
Infection Sepsis Severe Sepsis Septic Shock
Microbiological
Phenomenon
Infection
+
SIRS
Sepsis
+
End-Organ
Damage
Severe Sepsis
+
Refractory
Hypotension
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Sepsis: Pathophysiology
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Systemic
InflammationCoagulation
Impaired
Fibrinolysis
Sepsis: A complex disease
Sepsis
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Hemostasis is unbalanced in
severe sepsis
Hemostasis
Coagulation
InflammationFibrinolysis
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Sepsis: Pathophysiology
Micro-organism
Microbial Products
Host Inflammatory Mediators
Inflammation Coagulation
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Sepsis: PathophysiologyFinal Common Pathway
Endothelial Cell Injury &
Microvascular Thrombosis
Hypoperfusion/Ischemia
Acute Organ Dysfunction
Death
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Surviving Sepsis Campaign
Crit Care Med 2008 Reprint
Also published in Intensive Care Medicine
(January 2008)
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Management of Severe Sepsis :
Antibiotics
Source control
Hemodynamic support
Mechanical ventilation
Nutritional support
Renal replacement Rx
Activated Protein C
(Xigris)
Fluid resuscitation
Intensive
Insulin Tx
Low Dose
Steroids
Early
Goal-Directed Rx
Initial Resuscitation
• Fluid resuscitation as soon as sepsis suspected
• Should not wait until ICU admission
• Elevated lactate identifies tissue
hypoperfusion in at-risk patients who are not
hypotensive
• Resuscitation goals: EGDT
Rivers et al. NEJM 2001;345:1368-77
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SIRS
Sepsis Septic ShockSevere Sepsis
Golden hours
Early goal-directed therapy in severe
sepsis & septic shock
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From Dellinger RP. Cardiovascular management of septic shock. Crit Care Med 2003;31:946-955.
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• Involves manipulation of cardiac preload, afterload, and contractility to achieve a balance between systemic oxygen delivery and oxygen demand
• Resuscitation end points: CVP, BP, venous oxygen saturation, arterial lactate concentration
Early goal-directed therapy in severe
sepsis & septic shock
N Engl J Med 2001;345:1368-77
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Central venous and
arterial catheterization
CVP
8 -12 mm Hg
MAP
65 and 90 mm Hg
ScvO2
70%
Goals achieved
Hospital admission
Protocol for Early Goal-Directed Therapy
Crystalloid
Colloid
Vasoactive
agents
Transf. of RBC
until Hct 30%
Inotropic agents
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49.2%
33.3%
0
10
20
30
40
50
60
Standard Therapyn=133
EGDTn=130
P = 0.01*
28-day Mortality
Rivers E. N Engl J Med 2001;345:1368-77.
Early Goal-Directed Therapy Results
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Fluid Therapy
• Colloid or crystolloid resuscitation is considered equal
– Natural or artificial colloids (less peripheral edema)
– Crystalloids (less cost)
• Fluid challenge over 30 min
– 500-1000 ml crystalloid
– 300–500 ml colloid
• Target CVP 8 mm Hg (12 mm Hg in mechanically ventilated patients)
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Vasopressors
• Norepinephrine or dopamine through a central
catheter is the initial vasopressor of choice.
– Failure of fluid resuscitation
– During fluid resuscitation attempts
• Do not use low-dose dopamine for renal protection
• In patients requiring vasopressors, place an arterial
catheter as soon as possible
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Vasopressin and Septic Shock
•• Decreases or eliminates requirements of
traditional pressors
• As a pure vasopressor, expected to decrease
cardiac output
• Consider in refractory shock despite high dose
conventional vasopressors
• 0.01-0.04 units/minute in adults
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Inotropic Therapy
• Consider dobutamine in patients with measured
low cardiac output despite fluid resuscitation.
• Continue to titrate vasopressor to mean arterial
pressure of 65 mm Hg or greater.
• Do not increase cardiac index to achieve an
arbitrarily predefined elevated level of oxygen
delivery.
Corticosteroids
• IV hydrocortisone 200-300 mg/d for 7 days
– recommended in patients with septic shock
who, despite adequate fluid replacement,
require pressors to maintain adequate BP
– Decreased mortality in patients with relative
adrenal insufficiency
Annane et al. JAMA 2002;288:862-71
Briegel et al. Crit Care Med 1999;27:723-32
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Controversies and Future Directions
1. How generalizable is EGDT to other populations?
2. How cost-effective is EGDT?
3. How are time and resources utilized so that the
EGDT protocol is accomplished?
4. Which components of EGDT actually make a
difference in outcomes?
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Mortality Reduction
• 2006 analysis of available randomized and observational data from 12 centers, totaling 1,298 patients, yielded similar results
– Mortality was reduced from 44.8% in the control group to 24.5% in the EGDT group
• This is better than aspirin + streptokinase for MI 5-week mortality (NNT=19) or tPA for acute ischemic stroke within 4.5 hours (NNT=15)
CHEST 2006; 130; 1579-1595.
for every 5 EGDT patients, one life was
saved
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EGDT decreases health care resource
consumption
• Decrease in vasopressor use, hospital and
ICU LOS, and MV days
• With a long ED wait time for an ICU bed,
there are few options other than making this
an ED intervention
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Take home message
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Employ EGDT & Sepsis Bundles in the
treatment of severe sepsis and septic
shock
• if you want to save lives,
• save your institution money,
• improve your department’s
standing in the house of medicine
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Thank You